In recent years, a vitamin D having a hydroxy group at 1 .alpha. position, for example, 1.alpha.-hydroxy-vitamin D.sub.3 or 1.alpha.,25-dihydroxy-vitamin D.sub.3 has been given attention due to its strong vitamin D activities.
However, since vitamin D is usually used in a very small dose per single administration, it is difficult to give a predetermined exact amount per unit dose in case the vitamin D is formulated in the form of pill or tablet. Further, vitamin D is very sensitive to exposure to light, particularly to ultraviolet light and, therefore, its handling or treatment should be effected under light-intercepted conditions and also a pharmaceutical preparation containing the vitamin D should be stored without exposure to light.
From the viewpoint of stability of the vitamin D, the most desirable process for manufacturing a pharmaceutical preparation is to dissolve 1.alpha.-hydroxy-vitamin D in an oily diluent and then encapsulate the solution with a soft capsule.
The encapsulation in a soft gelatin capsule is advantageous because the press-through-pack can be employed with the use of transparent plastic film capable of intercepting ultraviolet light to reduce the deactivation of the vitamin D due to the exposure to ultraviolet light.
However, the inventors of this invention experimentally found that, even in case 1.alpha.-hydroxy-vitamin D was dissolved in an oily diluent and encapsulated in a soft gelatin capsule and the capsule preparation was subjected to the press-through-pack to intercept ultraviolet light, a considerable amount of 1.alpha.-hydroxy-vitamin D contained in the preparation lost its vitamin D activities.
The inventors continued their study on such deactivation phenomenon to find that the phenomenon is induced due to the effect of a p-hydroxybenzoic ester which is conventionally incorporated into a soft gelatin capsule as a preservative for gelatin. On the other hand, since gelatin, the base material for a capsule is putrescible and especially, such putrefaction is accelerated in case a soft gelatin capsule contains a softening agent, such as glycerin, polyethylene glycol, propylene glycol or the like, for preventing the capsule from hardening, a preservative should be present in the capsule.
The inventors focused their study on the preservative for gelatin and found that sorbic acid or its salt which is a suitable preservative does not induce the deactivation of a 1.alpha.-hydroxy-vitamin D and, besides, heightens its stability. Based on these facts, they finally completed the present invention.